The structure and expression of various crystallin genes have been investigated in humans, mice, chicken, squid, and jellyfish. The human and mouse alphaB-, the chicken betaA3/A1- and the major squid crystallin genes have been fully sequenced; many other squid and one jellyfish crystallin genes have been cloned. Numerous cis-regulatory sites have been identified in the 5' flanking regions of alphaA-, alphaB-, betaB1-, and squid crystallin genes, all of which include sequences known to bind transcription factors found in many tissues and involved in the regulation of other genes. In this connection, at least seven different cDNAs encoding zinc fingers have been cloned from the mouse lens. One of these cDNAs encoding a protein called alphaA-CRYBP1 is implicated in the lens-specific expression of the mouse alphaA-crystallin gene and is similar to human MBP-1 and PRDII-BF1, which bind to the MHC class I and the beta-interferon gene regulatory elements, respectively. The alphaA-CRYBP1 binding site confers lens-preferred expression to the thymidine kinase promoter when tested in an SV40-transformed mouse lens epithelial cell line, but not in primary cultures of chicken lens cells. The chicken alphaA-crystallin gene was found to use at least one and possibly two different sequences further upstream than the alphaA-CRYBP1 site for its expression in the lens cells; one of these has a dyad of symmetry. The insert exon of the alphaA-crystallin gene was shown to be present among many mammals, indicating an early evolutionary appearance for this alternatively spliced coding sequence. The two gamma-crystallin genes were shown to be differentially expressed in lens, heart and brain in chicken embryos. The gamma1 gene is specialized for lens, while the gamma2 gene is preferentially expressed in non-lens tissues, consistent with gamma2 being the homologue of the argininosuccinate lyase gene. Finally, the chicken carbonic anhydrase II gene was shown to be regulated differently in lens and retina, and a functional promoter has been cloned.